Deciphering the role of Wnt/β-catenin and miR-214 in knee osteoarthritis: molecular and clinical insights

Waad A Samman; Esraa M Mosalam; Dalia S Saif; Mahmoud S Abdallah; Abdel-Aziz A Zidan; Amany Said Sallam; Shimaa Abdelsattar; Fatma Omar Khalil; Amany E Elashkar; Somia Mokabel Mohamed; Mohamed Al-Ghannam; Hend E Abo Mansour

doi:10.3389/fphar.2025.1507693

Deciphering the role of Wnt/β-catenin and miR-214 in knee osteoarthritis: molecular and clinical insights

Front Pharmacol. 2025 Feb 25:16:1507693. doi: 10.3389/fphar.2025.1507693. eCollection 2025.

Authors

Waad A Samman¹, Esraa M Mosalam^{2

3}, Dalia S Saif⁴, Mahmoud S Abdallah^{3

5}, Abdel-Aziz A Zidan⁶, Amany Said Sallam⁷, Shimaa Abdelsattar⁸, Fatma Omar Khalil⁹, Amany E Elashkar¹⁰, Somia Mokabel Mohamed¹¹, Mohamed Al-Ghannam¹², Hend E Abo Mansour^{2

13}

Affiliations

¹ Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, Saudi Arabia.
² Department of Biochemistry, Faculty of Pharmacy, Menoufia University, Shebin EL-Kom, Menoufia, Egypt.
³ Department of Pharm D, Faculty of Pharmacy, Jadara University, Irbid, Jordan.
⁴ Department of Rheumatology, Physical Medicine, and Rehabilitation Department Faculty of Medicine, Menoufia University, Shebin EL-Kom, Menoufia, Egypt.
⁵ Department of Clinical Pharmacy, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufia, Egypt.
⁶ Zoology Department, Faculty of Science, Damanhur University, Damanhour, Egypt.
⁷ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Menoufia University, Shebin EL-Kom, Menoufia, Egypt.
⁸ Department of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shebin EL-Kom, Menoufia, Egypt.
⁹ Clinical Microbiology and Immunology Department, National Liver Institute, Menoufia University, Shebin EL-Kom, Menoufia, Egypt.
¹⁰ Clinical Pathology Department, National Liver Institute, Menoufia University, Shebin EL-Kom, Menoufia, Egypt.
¹¹ Department of Physiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
¹² Department of Radiology, Faculty of Medicine, Menoufia University, Shebin EL-Kom, Menoufia, Egypt.
¹³ Biochemistry Department, Faculty of Pharmacy, Menoufia National University, Birket El-Sab, Egypt.

Abstract

Introduction: Understanding the molecular mechanism underlying the pathogenesis of knee osteoarthritis (KOA) may be beneficial in fetching new therapeutics. Our study aims to investigate the implication of Wnt/ β-catenin pathway in development of KOA by detection of the downstream target genes and their crosstalk with miR-214 in patients with KOA and to correlate that with the clinical findings.

Methods: Sixty participants were involved in the study. The levels of miR-214, β-catenin, Wnt4, matrix metalloproteinase 3 (MMP3), Bax, caspase 3, and phosphorylated glycogen synthase kinase-3 beta (pGSK3β) were determined. All participants were assessed clinically and radiologically regarding knee joint pain, stiffness, range of motion, and knee medial cartilage thickness. Besides, a correlation between Western Ontario and McMaster Universities (WOMAC) score, clinical, and radiological data, and the measured parameters was conducted.

Results and discussion: Patients with KOA showed downregulated miR-214 with upregulated β-catenin, Wnt4, MMP3, Bax, caspase 3, and pGSK3β compared to healthy individuals. Statistically significant positive correlation between WOMAC score, knee joint pain regarding Visual Analogue Scale (VAS) with β-catenin, pGSK3β, Wnt4, MMP3, Bax, and caspase 3, and significant negative relationship between them and knee joint medial cartilage thickness; while there was a statistically significant negative correlation between WOMAC, and clinical findings of osteoarthritis and miR-214 and significant positive relationship between it and knee joint medial cartilage thickness. This study provides valuable insights into involvement of the Wnt/β-catenin and miR-214 in KOA pathogenesis. By targeting these molecular components, future therapeutics may modulate their activity and mitigate chondrocyte apoptosis and matrix degradation, potentially halting KOA progression.

Keywords: PGSK3β; WOMAC score; Wnt/β-catenin; knee osteoarthritis; miR-214.

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.